There is a paradigm shift in testing and modeling of chemical toxicity. Current toxicology calls for cell-based (vs. animal-based), evidence-based, and Omics-based assays. Mesenchymal stem cells (MSC) play important roles in the maintenance and repair of various tissues, including bone, cartilage, and muscle. MSCs are also found in circulating blood and participate in the wound-healing process. Therefore, MSC is arguably one of the most physiologically relevant adult stem cells for chemical toxicology. In response to RFA-ES-15-006, Newomics Inc. proposes this SBIR Phase II project to complete development of its product, high-throughput Omics-based assays to evaluate the effects of chemical toxicants on proliferation and differentiation of stem cells. The Phase II project is buil upon the extremely promising results generated from our Phase I project. In Phase I, we have demonstrated a robust and universal two-stage workflow for Omics-based and high-throughput screening of chemical toxicity using human MSCs. We have also discovered several pathways and networks for mechanistic understanding of chemical toxicity on MSCs. In Phase II, we will scale up our toxicity assays for MSCs using the Tox21 10k library, develop Omics-chips and validate their applications in Omics-based assays for chemical toxicity, and provide a toolkit for screening the effects of chemical toxicants on cell differentiation. Once developed, our platforms and solutions may be utilized for chemical toxicity studies of other types of stem cells such as ESCs and iPSCs, to help prioritize chemicals for in-depth toxicological evaluation, and to even help develop new intervention strategies for mitigating chemical toxicity, thereby contributing to public health.